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Pathogenesis and diagnosis of myeloma cast nephropathy (myeloma kidney)

INTRODUCTION

The term myeloma kidney or myeloma cast nephropathy refers to a disorder in which monoclonal urinary immunoglobulin light chains (Bence Jones proteins) lead to acute or chronic renal failure [1-3]. (See "Types of renal disease in multiple myeloma".) By definition, the diagnosis of light chain cast nephropathy indicates the presence of multiple myeloma; in other words, it is considered a "myeloma-defining event" [4]. Light chain cast nephropathy can occur as the first manifestation of myeloma or can develop later during the course of myeloma.

This topic provides a review of the pathogenesis and diagnosis of myeloma cast nephropathy. Overviews of the renal diseases associated with multiple myeloma and the therapy of acute renal failure (ARF) in multiple myeloma are discussed separately. (See "Types of renal disease in multiple myeloma" and "Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases" and "Treatment of kidney disease in multiple myeloma".)

PATHOGENESIS

Cast nephropathy is caused by large amounts of monoclonal free light chains (MFLCs) produced in multiple myeloma [5]. Light chains are freely filtered across the glomerulus and then largely reabsorbed by the proximal tubular cells. The normal rate of light chain excretion is <30 mg/day. However, reabsorptive capacity can be exceeded due to overproduction in multiple myeloma, resulting in an increase in light chain excretion that can range from 100 mg to >20 g/day.

The risk of cast nephropathy is directly related to the urinary free light chain (FLC) concentration and the type of light chains [6]. In an analysis of 2592 patients enrolled in multicenter myeloma trials, kidney injury developed in up to 54 percent of patients who had a high concentration of urinary FLC (defined as >12 g/g creatinine), but in only ≤2 percent of patients with no urinary light chains [7]. The risk of renal failure was approximately 8 to 18 and 29 to 38 percent among those who had urinary light chains of 0 to 4 and 4 to 12 g/g, respectively. However, urinary FLC measurements are rarely used in clinical practice since the test is unreliable. The methods used to estimate MFLC are the serum free light chain (SFLC) assay and the 24-hour urine protein electrophoresis. (See 'Diagnosis' below and "Recognition of monoclonal proteins".)

Cast nephropathy is uncommon in patients with low (<1500 mg/L) SFLC concentrations [8,9].

            

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Literature review current through: Sep 2014. | This topic last updated: Nov 21, 2013.
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